Such functional analyses have however, suggested that APOE is an agonist of TREM2 (Jendresen et al., 2017) and that several TREM2 variants associated with AD impair TREM2 activation whereas other variants opposingly increase TREM2 activation in response to phosphatidylcholine and other lipid ligands (Song et al., 2017) suggesting that AD TREM2 mutations are not simply loss of function mutations as previously thought. The gene discussed is APOE; the disease is Alzheimer disease.